Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Biochem Biophys Res Commun. 2014 Jan 10;443(2):712-7. doi: 10.1016/j.bbrc.2013.12.032. Epub 2013 Dec 12.
Salinomycin (Sal) is a polyether ionophore antibiotic that has recently been shown to induce cell death in various human cancer cells. However, whether salinomycin plays a functional role in nasopharyngeal carcinoma (NPC) has not been determined to date. The present study investigated the chemotherapeutic efficacy of salinomycin and its molecular mechanisms of action in NPC cells. Salinomycin efficiently inhibited proliferation and invasion of 3 NPC cell lines (CNE-1, CNE-2, and CNE-2/DDP) and activated a extensive apoptotic process that is accompanied by activation of caspase-3 and caspase-9, and decreased mitochondrial membrane potential. Meanwhile, the protein expression level of the Wnt coreceptor lipoprotein receptor related protein 6 (LRP6) and β-catenin was down-regulated, which showed that the Wnt/β-catenin signaling was involved in salinomycin-induced apoptosis of NPC cells. In a nude mouse NPC xenograft model, the anti-tumor effect of salinomycin was associated with the downregulation of β-catenin expression. The present study demonstrated that salinomycin can effectively inhibit proliferation and invasion, and induce apoptosis of NPC cells in vitro and inhibit tumor growth in vivo, probably via the inhibition of Wnt/β-catenin signaling, suggesting salinomycin as a potential candidate for the chemotherapy of NPC.
黏菌素(Salinomycin)是一种聚醚离子载体抗生素,最近已被证实可诱导多种人类癌细胞死亡。然而,黏菌素在鼻咽癌(NPC)中是否具有功能作用尚未确定。本研究旨在探讨黏菌素对 NPC 细胞的化疗疗效及其作用机制。黏菌素能有效抑制 3 种 NPC 细胞系(CNE-1、CNE-2 和 CNE-2/DDP)的增殖和侵袭,并激活广泛的凋亡过程,伴随着 caspase-3 和 caspase-9 的激活以及线粒体膜电位的降低。同时,Wnt 核心受体脂蛋白受体相关蛋白 6(LRP6)和 β-连环蛋白的蛋白表达水平下调,表明 Wnt/β-连环蛋白信号通路参与了黏菌素诱导的 NPC 细胞凋亡。在裸鼠 NPC 异种移植模型中,黏菌素的抗肿瘤作用与 β-连环蛋白表达的下调有关。本研究表明,黏菌素可有效抑制 NPC 细胞的增殖和侵袭,诱导细胞凋亡,并抑制体内肿瘤生长,可能通过抑制 Wnt/β-连环蛋白信号通路发挥作用,提示黏菌素可能成为 NPC 化疗的潜在候选药物。